We have isolated a growth-promoting serum tripeptide from human plasma and serum with the structure H-Gly-His-Lys-OH (GHL). Nanomolar concentrations of the synthetic GHL stimulate the growth in culture of numerous cell lines. Recent work suggests that GHL may function by mediating copper transport into cultured cells. We propose to study the metabolism and cellular distribution of H3-GHL in cultured cells and in vivo in rats. GHL-copper interactions will be studied by biological methods (e.g. effect on copper distribution) and chemical methods (e.g. X-ray structural analysis, electron paramagnetic resonance, nuclear magnetic resonance). The effect of a variety of blocked-analogs of GHL on cell growth will be determined.